BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007).

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

Assessment and management of dry eye disease.

The topic of the 1984 Cambridge Ophthalmological Symposium was 'The Dry Eye'; it was chaired by my colleague and mentor Mr Peter Wright. In the 33 years that have passed since then we have learned a great deal more about this condition. This short paper sets out to review some of the more recent developments.

Macrophage polarisation affects their regulation of trophoblast behaviour.

INTRODUCTION: During the first trimester of human pregnancy, fetally-derived extravillous trophoblast (EVT) invade into the uterine decidua and remodel the uterine spiral arteries to ensure that sufficient blood reaches the maternal-fetal interface. Decidual macrophages have been implicated in the regulation of decidual remodelling, and aberrant activation of these immune cells is associated with pre-eclampsia. METHODS: The monocytic cell line THP-1 was activated to induce a classically- or alternatively-activated macrophage phenotype and the conditioned media was used to treat the EVT cell line SGHPL-4 in order to determine the effect of macrophage polarisation on trophoblast behaviour in-vitro. SGHPL-4 cell functions were assessed using time-lapse microscopy, endothelial-like tube formation assays, and western blot. RESULTS: The polarisation state of the THP-1 cells was found to differentially alter the behaviour of trophoblast cells in-vitro with pro-inflammatory classically-activated macrophage conditioned media significantly inhibiting trophoblast motility, impeding trophoblast tube formation, and inducing trophoblast expression of cleaved caspase 3, when compared to anti-inflammatory alternatively-activated macrophage conditioned media. DISCUSSION: Macrophages can regulate trophoblast functions that are critical during decidual remodelling in early pregnancy. Importantly, there is differential regulation of trophoblast function in response to the polarisation state of these cells. Our studies indicate that the balance between a pro- and anti-inflammatory environment is important in regulating the cellular interactions at the maternal-fetal interface and that disturbances in this balance likely contribute to pregnancy disorders associated with poor trophoblast invasion and vessel remodelling.

Contact clinical specular microscopy of the corneal endothelium: optical modifications to the applanating objective cone.

The value of clinical specular microscopy of the corneal endothelium has been limited by the extremely small field of view of the image obtained. This is largely a result of an overlying brilliant reflection from the objective (or air)/cornea interface. A modification to the applanating objective cone of the contract specular microscope is described, which virtually eliminates this reflection and gives a visible field of almost 1 mm2 of the endothelium. The theory behind the objective modification is presented, and other advantages of the system, such as reduction of eye movement, are noted.

The immunomodulatory effect of topical cyclosporin A in atopic keratoconjunctivitis.

PURPOSE: To perform a detailed examination of the immunomodulatory effects of topical cyclosporin A (CsA) in conjunctival tissue from patients with atopic keratoconjunctivitis (AKC). METHODS: Patients with active AKC were randomly allocated into two groups of four patients. For 3 months one group received 2% CsA drops, and the other group received placebo drops. Superior tarsal conjunctival biopsy specimens were harvested before and after treatment and examined by one- and two-color immunohistochemistry to compare leukocyte counts, HLA-DR+ and IL-2R+ cell counts, HLA-DR positivity of conjunctival epithelial cells, and counts of T cells expressing the cytokines interleukin (IL)-2, IL-3, IL-4, IL-5, and interferon (IFN)-gamma. RESULTS: Posttreatment values were significantly less than pretreatment values for the total number of leukocytes and in the numbers of CD3+ T cells, CD4+ cells, CD8+ cells, CD20+ B cells, neutrophils, and macrophages, and there was a decrease in the CD4-CD8 ratio (P = 0.03) in the CsA group. There was a reduction from before CsA treatment to after CsA-treatment in the numbers of HLA-DR+ and IL-2R+ cells (P = 0.03), but the reduction in the epithelial cell HLA-DR expression did not reach significance. The number of T cells staining for IL-3 and IL-5 was reduced, although not to statistical significance, but there was a significant reduction in the number of T cells expressing IL-2 and IFN-gamma (P = 0.03) after CsA treatment compared with initial values. There were no statistically significant differences between pretreatment and posttreatment values in the placebo group. There was a clinical improvement in the CsA group and a clinical worsening in the placebo group. CONCLUSIONS: The in vitro effects of CsA translate into a reduction in T cells, a normalization of the CD4-CD8 ratio, a decrease in T-cell activation, and a reduction in T-cell cytokine expression, especially IL-2 and IFN-gamma. The decrease in HLA-DR expression may be mediated by the change in IFN-gamma. There were fewer B cells but not fewer plasma cells after CsA and no change in IL-4 expression, suggesting minimal effects on type I hypersensitivity responses. There was no significant reduction in mast cell or eosinophil numbers, but direct effects of topical CsA on their function may play a role in the therapy of ocular allergic disease. These results show that the beneficial effects of topical CsA in AKC are accompanied by important changes in conjunctival immune cell profiles.

The relief mode. New application of the corneal specular microscope.

The growing clinical use of specular microscopy for the examination of the corneal endothelium demands accurate interpretation of the various abnormalities or "events" encountered in the specular image of diseased endothelia. In a new method of use of a large-field specular microscope, extensive areas of the posterior surface of the cornea may be viewed in apparent relief. In this "relief mode," any entities causing events in the specular image that interrupt the smooth posterior contours of the cornea can be seen by diffuse (as opposed to specularly reflected) light, and their true size, shape, and interrelationships are clearly shown. The relief and specular images occur in the same field of view and thus allow immediate elucidation of the nature of most events.

Ocular chloramphenicol and aplastic anaemia. Is there a link?

The question of a link between the use of topical ocular chloramphenicol and the incidence of aplastic anaemia continues to be a controversial issue in ophthalmological spheres. At present topical ocular chloramphenicol is widely used in the UK for the treatment of conjunctivitis, whereas it is very rarely prescribed for this indication in the U.S. Individual policies vary around the rest of the world. The evidence for and against any association between topical and ocular chloramphenicol and an increased risk of aplastic anaemia is reviewed, and the reasons behind the current prescribing policies are clarified. The discussion generated in the literature over the past 2 years over this issue is considered, along with the published debate from the past 3 decades. The debate is not conclusive, but by presenting or referencing the specific case reports and the published opinions of various experts, we hope to enable the reader to make his or her own informed decision as to whether use of the topical preparation of chloramphenicol should be considered by the ophthalmological community.

Eosinophil granule major basic protein deposition in corneal ulcers associated with vernal keratoconjunctivitis.

An indirect immunofluorescence assay detected eosinophil granule major basic protein in the inflammatory debris covering deepithelialized cornea in two patients with vernal keratoconjunctivitis. A slight degree of non-specific fluorescence was present in the control autopsy corneas. High concentrations of the eosinophil granule major basic protein inhibit epithelial migration and protein synthesis, whereas low concentrations affect epithelial migration. The results suggest participation of eosinophil granule major basic protein in the ulcerative process.

Mental confusion in a patient treated with metronidazole--a concentration-related effect?

We report a case of serious mental confusion, hallucinations, and agitation in a 65 year old man, occurring in close relationship to the intravenous administration of metronidazole. The patient was treated twice, but at different dosages. The confusion and hallucinations occurred at the recommended daily dose of 2.0 g, but did not return at a daily dose of 500 mg. Metronidazole serum concentrations were obtained throughout both courses of therapy; CSF and tissue concentrations were obtained at autopsy. The mental confusion was associated with peak serum concentrations of approximately 40 micrograms/ml. Symptoms resolved within 24-48 hr after stopping metronidazole, and resolution was consistent with a metronidazole half life of 14 hr. We conclude that metronidazole can be associated with a dose- and serum concentration-related mental confusion state, and that this side effect appears completely reversible upon discontinuing the drug.

Relocation of specific endothelial features with the clinical specular microscope.

The selection and later relocation of specific areas of the in-vivo human corneal endothelium at relatively high magnification with a clinical specular microscope are demonstrated by case examples. Relocation of an area of the endothelium is greatly facilitated by the large field of view, the reduction of eye movement, and the presence of posterior corneal rings, induced by applanation of the cornea, which serve as a target system.

Pathogenesis and treatment of recurrent erosion.

A series of recurrent corneal erosions secondary to map-dot-fingerprint dystrophy is presented. Erosions were closely related to the Hudson-Stahli line, and this may be a factor in pathogenesis. Traumatic abrasions did not demonstrate such localisation, evidence that trauma is not a primary cause. A trial of management with therapeutic contact lenses versus topical medication was performed. Therapeutic contact lenses were shown to be inferior and had a high complication rate. Recurrent erosion is often considered an indication for therapeutic contact lenses, but this is questioned and great caution recommended in such use.

Myopia following penetrating keratoplasty for keratoconus.

The frequent occurrence of spherical myopia after penetrating keratoplasty for keratoconus is partly the result of the excessive dioptric power of the grafted cornea which occurs when the diameter selected for the donor button is greater than the diameter of the host incision. This excessive power could be reduced by eliminating disparity between the diameters of the graft and host. To determine what proportion of the myopia in these eyes would persist as a result of axial myopia the axial lengths of 60 patients grafted for keratoconus and 25 emmetropic controls were compared. A keratometry, objective refraction, and contact probe ultrasonic biometry were performed on all eyes. A comparison of the results with a representational schematic eye indicated that the mean spherical refractive error of the grafted keratoconic eyes (-4.83 dioptres) was the combined effect of steepness of the corneal graft (mean radius of curvature 7.46 mm) and an abnormally great axial length (mean 24.84 mm). The increased axial length was mainly the result of elongation of the posterior segment of the globe with a small contribution from an increased anterior chamber depth. Though axial myopia is common in keratoconus, a further study of 70 keratoconic eyes that had not been grafted showed no statistically significant correlation between the posterior segment length and the severity of corneal ectasia. These data suggest that even if excessive corneal power is eliminated after penetrating keratoplasty for keratoconus the associated axial myopia would still produce a mean spherical refractive error of at least -2.8 dioptres.

Intrascleral neurilemmoma.

The case of an anteriorly situated, intrascleral, neurilemmoma in an 11-year-old girl is reported. Only two similar cases have been described in the literature, and the diagnosis was made only after detailed histological examination, including electron microscopy and specialised staining techniques, to differentiate a neurilemmoma (schwannoma) from a neurofibroma.

Distinguishing features of the iridocorneal endothelial syndrome and posterior polymorphous dystrophy: value of endothelial specular microscopy.

The literature suggests that posterior polymorphous dystrophy (PPD) may show features such as iridocorneal adhesions, glassy membranes, and pupillary ectropion which are typically ascribed to the iridocorneal endothelial (ICE) syndrome. This complicates diagnosis. PPD, unlike ICE, is familial, and ICE, unlike PPD, is usually progressive and frequently complicated by glaucoma: thus it is important to distinguish between them. To determine whether this could be achieved by specular microscopy, since the posterior corneal surface is abnormal in both conditions, 57 cases of ICE and 44 of PPD were repeatedly examined and photographed with the specular microscope. Progressive and/or static morphological features of the corneal endothelium and Descemet's membrane were found that were specific for each condition. Specular microscopy can thus provide a definitive diagnosis of ICE or PPD even in uncertain cases.

Life expectancy in keratoconus.

It is observed that few patients over the age of 60 regularly attend the keratoconus clinic at Moorfields Eye Hospital. The hypothesis that patients with keratoconus have a shorter life expectancy owing to underlying connective tissue related disease was tested. From patient records a sample of 337 keratoconus patients aged at least 40 years by 1991 were identified, of which 279 were living, 13 were deceased, and 45 were untraceable. The mortality rate for keratoconus patients was compared with that of the general population using actuarial English life tables. Results show no significant difference between the general population mortality rate and that of the keratoconus sample even with adjustment for social class. Possible explanations for the non-attendance of older patients are discussed.

Comparative intraocular penetration of topical and injected cefuroxime.

AIMS: The choice of a prophylactic antibiotic for cataract surgery is dependent on its antibacterial activity and tissue penetration. The influence of the route and timing of administration of cefuroxime on its intraocular concentrations was examined. METHODS: 120 patients were recruited before cataract surgery into a prospective trial to compare the anterior chamber concentration of cefuroxime at a fixed time after administration by three routes. In a further 110 patients, the interval before sampling was varied in order to permit an examination of the kinetics of penetration. In another 10 patients, cefuroxime was given topically at the completion of surgery to assess the effect of a corneal wound on aqueous penetration. Cefuroxime concentrations were measured by high performance liquid chromatography on 0.2 ml samples of aqueous aspirated from the anterior chamber. Mean aqueous concentrations of cefuroxime for each group were compared using Student's t test. RESULTS: After 25 mg cefuroxime, mean aqueous concentrations increased in the order forniceal (< 0.1 microgram/ml) < topical (0.18 microgram/ml) < subconjunctival (2.31 microgram/ml) when sampled 12-24 minutes after administration. Aqueous concentrations of cefuroxime reached a peak between 80 and 110 minutes after both forniceal and peribulbar injection but were still rising at this time after subconjunctival injection. Topical application of 12.5 mg cefuroxime to eyes with a 10 mm corneal wound resulted in a mean aqueous concentration of 9.34 micrograms/ml. CONCLUSION: In the intact eye, only sub-conjunctival injection resulted in clinically significant aqueous concentrations of cefuroxime (> 1 microgram/ml) between 12 and 24 minutes after administration. For all routes, maximal aqueous concentrations were delayed by at least 80 minutes from administration. In the presence of a corneal wound, high aqueous levels of cefuroxime were rapidly attained after topical application.

Minimising the risk of prion transmission by contact tonometry.

AIMS: The unknown prevalence of variant Creutzfeldt-Jakob disease (vCJD) in the UK population has led to fears of horizontal transmission through routine medical procedures. The potential risk of transmission via contact tonometry was examined. METHODS: The total amount of protein carried over by tonometer tips after applanation of patients was assessed. RESULTS: Tonometer tips had an inherent ability to carry proteinaceous material. There was a large variability in the load carried over between individual patients. Rinsing tonometer tips in water reduced protein carryover. Wiping the tonometer tips also reduced carriage, though less dramatically. CONCLUSION: There is a small theoretical risk of transmission of vCJD by contact tonometry through reuse, but this should be reduced if the prisms are washed and wiped. In the light of these findings a protocol for the management of reusable tonometer prisms is recommended.

Systemic cyclosporin A in high risk penetrating keratoplasties: a case-control study.

AIM: To examine the efficacy of systemic cyclosporin A (CSA) in preventing rejection and graft failure in high risk keratoplasty (PK). METHODS: A retrospective case-control study with 49 patients in both the CSA group and the control group. The patients receiving CSA were at high risk of graft rejection and failure. Controls were identified from surgical audit books and had high risk characteristics. RESULTS: There was no statistical difference in preoperative risk factors and the use of postoperative topical steroids between the two groups. The median follow up in the CSA group was 22 months and 27 months in the control group. One or more rejection episodes occurred in 18 out of 49 (36.7%) cases in the CSA group and 26 out of 49 (53.1%) in the control group. Graft failure from all causes occurred in 16 (32.7%) CSA patients and 18 (36.7%) control patients. Four (8.2%) of the CSA group compared to eight (16.3%) in the control group failed because of rejection. 22 (44.9%) out of 49 patients in the CSA group had side effects. In five (10.2%) patients, CSA was stopped because of the side effects; eight patients had elevated serum urea and creatinine and four developed hypertension. Minor side effects reported include gum hyperplasia, increased sweating, backache, nausea, feeling unwell, oral candidiasis, cramps, and paraesthesia of the extremities. CONCLUSION: These results suggest that the benefit of CSA over conventional therapy in preventing rejection episodes and subsequent graft failure is only moderate and did not reach statistically significant levels in this study. Considering the high frequency of side effects and the cost of CSA, a randomised control trial may be necessary to determine the true value of CSA in high risk penetrating keratoplasty.

Iris ischaemia following penetrating keratoplasty for keratoconus (Urrets-Zavalia syndrome)

A fixed and dilated pupil is an uncommon postoperative complication after penetrating keratoplasty (PK) for keratoconus. Although the clinical features have been well described, the precise aetiology is uncertain. We performed anterior segment fluorescein angiography in the early postoperative period on three patients who developed fixed, dilated pupils after apparently uncomplicated surgery. All of the eyes had severe iris ischaemia. A possible role for a postoperative rise in intraocular pressure in the aetiology of this syndrome is discussed.

A study of 530 patients referred for rigid gas permeable scleral contact lens assessment.

PURPOSE: The purpose of this study was to analyse the current application of scleral contact lenses in two specialist centres. METHODS: The case notes of 530 patients assessed for fitting or refitting with rigid gas permeable (RGP) scleral lenses were retrospectively analysed to determine the indication for contact lenses and the outcome. Scleral lenses had been offered as a conservative management option in suitable cases for a variety of visual and medical indications. RESULTS: Various types of primary corneal ectasia, ranging from low grade to advanced, including keratoconus, keratoglobus, and pellucid marginal degeneration, formed 53.0% of the total referred for assessment. The other principal indications for contact lenses were corneal transplant (15.8%), aphakia (10.3%), high myopia (8.9%), and various ocular surface disorders (8.2%). Sixty percent continued to use scleral lenses, 42.9% RGP, and 17.1% polymethylmethacrylate lenses. Twenty-two percent discontinued scleral lens wear or failed a trial of scleral lenses, with 9.3% in progress at the time of assessment and 8.7% lost to follow-up. CONCLUSIONS: In the authors' opinion, scleral lenses have retained their traditional role in the management of complex ametropia and ocular surface disease. That role has been further enhanced by the application of gas permeable materials.